Timothy Ray Brown has become the first known case of a person "cured" of the HIV virus. The cure came thanks to a chemotherapy treatment for a cancer he developed and a subsequent stem cell transplant. (Source: Stern)

The success may eventually be able to replicated in others that suffer from HIV, but it will likely be very expensive. (Source: South Park Studios/Comedy Central)

Timothy Brown shows no trace of HIV since his stem cell transplant in the summer of 2006. (Source: www.peterrigaud.com)

Caustic cancer treatment regimen, combined with a clever genetic trick kicked the pesky HIV virus out for good

Timothy Ray Brown might seem very unfortunate if you knew some aspects of his medical story. A U.S. citizen living abroad in Berlin, Mr. Brown was diagnosed with acute myeloid leukemia.

As the disease spread through his bone marrow, he was forced to undergo grueling chemotherapy and then a stem cell transplant. Then the disease flared up yet again, forcing yet another stem cell transplant.

Finally recovering, he then suffered an unexpected neurological side effect, which left him forgetful and temporarily blind. He had to undergo therapy just to be able to try to walk and talk normally.

But the treatment did something incredible, something that has never before been documented in the modern medical community -- it cured Mr. Brown of the human immunodeficiency virus -- better known as HIV.

Deadly, but Effective

Approximately 1 percent of Caucasians in northern and western Europe have a special mutation that virtually prevents them from being infected with the HIV virus. The mutation, dubbed CCR5 delta 32 homozygosity, causes individuals to lack the CCR5 receptor, which the HIV lentivirus uses to accomplish its infection process.

Physicians treating Mr. Brown's cancer purposefully selected a donor who happened to have this beneficial mutation.

Hopes of a cure seemed faint, though. After all, if the HIV infection in Mr. Brown's former CD4 (T-cell) population had advanced enough, it would have developed the ability to infect using the CXCR4 receptor, rendering the protective mutation useless. And even if the virus had not armed itself with this new ability, no one had ever been cured of the disease.

While Mr. Brown may have been unfortunate by and large medically, he apparently lucked out when it came to his HIV infection.

Taken abruptly off antiretroviral drugs after the transplant, he showed no signs of HIV infection. For the next 38 months he underwent immunosuppressive treatment to protect the graft as it repopulated his intestinal mucosa.

Tissue samples taken during this time period showed spiking levels of the donor T-cells and no trace of infection. Weaning off immunosuppressants, the man's T-cell levels dropped to that of a healthy adult male.

Medical researchers concluded that it was unlikely that the man still had HIV -- after all if he had the disease, it would have likely evolved the CXCR4 infection ability and infected his immunotransplant.

Further evidence the disease was gone was shown by dropping levels of his body's HIV antibodies. And viral load testing (RNA) and tests for viral DNA within cells -- two tests that typically reveal the presence of HIV -- came back negative.

Can Doctors Replicate This Unusual Success?

Mr. Brown's ordeal was chronicled in the German magazine Stern.

The results have also been published in an article in the peer-reviewed journal Blood and a study [PDF] in The New England Journal of Medicine.

As the magazine notes, past attempts to graft "immune" T-cells failed, due to the long lifespans of the victim's infected T-cells. Those long lifespans bought the virus enough time to mutate and overcome the graft's immunity. But in Mr. Brown's case, the chemotherapy killed enough of the infected cells that the mutation was not able to occur.

While the treatment regiment is extremely dangerous, chemotherapy -- long aimed at curing cancer -- may soon be used to cure HIV.

The key remaining obstacle is to develop ways to create CCR5 deficient T-cells.

Mr. Brown was fortunate in that a donor was found who happened to have this mutation. Most won't be that lucky. But researchers are hoping to create stem cells from the patient's various cell lines, differentiate them into T-cells, and finally using gene therapy to knock out the CCR5 receptor DNA.

The resulting treatment may not be correct for everybody. HIV is largely repressible with today's advanced drug regimens. Some may decline to risk their lives to be pronounced "cured".

For those who may someday opt for this route, the resulting treatment will likely be very expensive. Thus South Park's irreverent recent episode "Tonsil Trouble", which depicted NBA-great Magic Johnson being "cured" of HIV via a money transfusion may prove somewhat prophetic.

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quote: Hopes of a cure seemed faint, though. After all, if the HIV infection in Mr. Brown's former CD4 (T-cell) population had advanced enough, it would have developed the ability to infect using the CXCR4 receptor, rendering the protective mutation useless. And even if the virus had not armed itself with this new ability, no one had ever been cured of the disease.

...and

quote: Medical researchers concluded that it was unlikely that the man still had HIV -- after all if he had the disease, it would have likely evolved the CXCR4 infection ability and infected his immunotransplant.

My understanding is that the CCR5 variant of the virus is the primary one transmitted by infection. Thus newly infected persons could likely undergo this treatment, before their infection mutated, as I suggested...

HIV is sadly pretty complex, with numerous subtypes. Only subtype B is obligate to use the CCR5 receptor from the start, so it's diminished in infectivity by at least 70% when this d32 mutation is heterozygous, and basically completely stopped when homozygous. Other subtypes use the CD4, and the CCR2 and CCR5 receptors in the beginning, which allows them to be somewhat resistant to this mutation.

I watched a documentary many years ago where they traced a genetic mutation in modern people immune to HIV, showing them to be the descendants of Europeans who survived the bubonic plague during the Dark Ages.

As for the absence of HIV in this case, is it possible that the treatment reset the infection such that it is lying dormant like it typically does during the initial stages? Even so, assuming the immune system was not wiped out during the aggressive chemotherapy treatment, then HIV should not be able to build up sufficiently to push past equilibrium into full-blown AIDS when the immune system is put under stress from other non-HIV sources.

CCR5 is the only strain spread sexually or through blood. CXCR4 is a mutation that occures once infected and does not leave the body. CCR5 and CXCR4 co-exist in those with CCR5 infections, and work together resulting in AIDS. If you lack CCR5 receptors, you can not be infected with HIV.

However, there are over 80 mutations of HIV and we are only talking about one.